A neuroepithelial wave of BMP signalling drives anteroposterior specification of the tuberal hypothalamus

Abstract

The tuberal hypothalamus controls life-supporting homeostatic processes, but despite its fundamental role, the cells and signalling pathways that specify this unique region of the CNS in embryogenesis are poorly characterised. Here we combine experimental and bioinformatic approaches in the embryonic chick to show that the tuberal hypothalamus is progressively generated from hypothalamic floor plate-like cells. Fate-mapping studies show that a stream of tuberal progenitors develops in the anterior-ventral neural tube as a wave of neuroepithelial-derived BMP signalling sweeps from anterior to posterior through the hypothalamic floor plate. As later-specified posterior tuberal progenitors are generated, early-specified anterior tuberal progenitors become progressively more distant from these BMP signals and differentiate into tuberal neurogenic cells. Gain- and loss-of-function experiments in vivo and ex vivo show that BMP signalling initiates tuberal progenitor specification, but must be eliminated for these to progress to anterior neurogenic progenitors. ScRNA-Seq profiling shows that tuberal progenitors that are specified after the major period of anterior tuberal specification begin to upregulate genes that characterise radial glial cells. This study provides an integrated account of the development of the tuberal hypothalamus.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file.All chick single-cell RNA-seq data have been deposited at GEO (GSE171649) and are publicly available.

The following data sets were generated

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Author details

  1. Kavitha Chinnaiya

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3375-420X
  2. Sarah Burbridge

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Aragorn Jones

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4255-2482
  4. Dong Won Kim

    Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8624-0168
  5. Elsie Place

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Elizabeth Manning

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Ian Groves

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Changyu Sun

    Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Matthew Towers

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2189-4536
  10. Seth Blackshaw

    Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1338-8476
  11. Marysia Placzek

    Department of Biomedical Science, University of Sheffield, Sheffied, United Kingdom
    For correspondence
    m.placzek@sheffield.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4106-9229

Funding

Wellcome Trust (212247/Z/18/Z)

  • Marysia Placzek

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Elisabeth Knust, Max-Planck Institute of Molecular Cell Biology and Genetics, Germany

Version history

  1. Received: August 31, 2022
  2. Preprint posted: September 2, 2022 (view preprint)
  3. Accepted: January 29, 2023
  4. Accepted Manuscript published: January 31, 2023 (version 1)
  5. Version of Record published: February 10, 2023 (version 2)

Copyright

© 2023, Chinnaiya et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kavitha Chinnaiya
  2. Sarah Burbridge
  3. Aragorn Jones
  4. Dong Won Kim
  5. Elsie Place
  6. Elizabeth Manning
  7. Ian Groves
  8. Changyu Sun
  9. Matthew Towers
  10. Seth Blackshaw
  11. Marysia Placzek
(2023)
A neuroepithelial wave of BMP signalling drives anteroposterior specification of the tuberal hypothalamus
eLife 12:e83133.
https://doi.org/10.7554/eLife.83133

Share this article

https://doi.org/10.7554/eLife.83133

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